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1.
IEEE Trans Biomed Eng ; PP2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768001

RESUMO

Freezing of gait (FOG) leads to an increased risk of falls and limited mobility in individuals with Parkinson's disease (PD). However, existing research ignores the fine-grained quantitative assessment of FOG severity. This paper provides a double-hurdle model that uses typical spatiotemporal gait features to quantify the FOG severity in patients with PD. Moreover, a novel multi-output random forest algorithm is used as one hurdle of the double-hurdle model, further enhancing the model's performance. We conduct six experiments on a public PD gait database. Results demonstrate that the designed random forest algorithm in the double-hurdle model-hyperparameter independence framework achieves outstanding performances with the highest correlation coefficient (CC) of 0.972 and the lowest root mean square error (RMSE) of 2.488. Furthermore, we study the effect of drug state on the gait patterns of PD patients with or without FOG. Results show that "OFF" state amplifies the visibility of FOG symptoms in PD patients. Therefore, this study holds significant implications for the management and treatment of PD.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38757624

RESUMO

Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.

3.
Sci Total Environ ; 933: 172875, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38703839

RESUMO

Dry direct-seeded rice cultivation has gained popularity and expanded its cultivated area due to reduced labor requirements and water consumption. However, the impact of this cultivation method on cadmium (Cd) bioavailability in soil and the accumulation levels in grains remains uncertain. Field experiments were conducted in acidic soils at two locations in southern China to compare rice varieties and evaluate the dry direct-seeding method alongside the wet direct-seeding and traditional transplanting methods. Dry direct-seeded rice reached significantly higher Cd concentrations in its tissues starting from the heading stage than transplanted rice. Cd accumulation levels by the maturation stage in the brown rice of dry direct-seeded rice were 18.33 %-150.69 % higher than those of wet direct-seeded and transplanted rice, with a considerable ability to translocate Cd into brown rice. Furthermore, dry direct seeding decreased iron plaque formation, particularly in the amorphous Fe form; it resulted in high soil temperature and low moisture content during tillering, elevating Cd availability in the soil. Additionally, the proportion of ions and more labile forms of Cd in the soil solution was high. Moreover, the soil under dry direct seeding had high urease and acid phosphatase enzyme activities. However, low richness and diversity in the bacterial community were characterized by a significant increase in the relative abundance of Actinobacteria and Gammaproteobacteria at the class level, while exhibiting decreased relative abundances of Alphaproteobacteria, Bacilli, and KD4-96, along with fewer biomarkers. Nonetheless, these differences are gradually reduced during the maturation stage. Overall, although dry direct seeding offers several advantages, it is crucial to implement additional measures to mitigate the increased health risks linked to rice cultivation through this approach in Cd-contaminated areas.

4.
Nanoscale ; 16(19): 9317-9324, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38656387

RESUMO

For atomically thin two-dimensional materials, variations in layer thickness can result in significant changes in the electronic energy band structure and physicochemical properties, thereby influencing the carrier dynamics and device performance. In this work, we employ time- and energy-resolved photoemission electron microscopy to reveal the ultrafast carrier dynamics of PdSe2 with different layer thicknesses. We find that for few-layer PdSe2 with a semiconductor phase, an ultrafast hot carrier cooling on a timescale of approximately 0.3 ps and an ultrafast defect trapping on a timescale of approximately 1.3 ps are unveiled, followed by a slower decay of approximately tens of picoseconds. However, for bulk PdSe2 with a semimetal phase, only an ultrafast hot carrier cooling and a slower decay of approximately tens of picoseconds are observed, while the contribution of defect trapping is suppressed with the increase of layer number. Theoretical calculations of the electronic energy band structure further confirm the transition from a semiconductor to a semimetal. Our work demonstrates that TR- and ER-PEEM with ultrahigh spatiotemporal resolution and wide-field imaging capability has great advantages in revealing the intricate details of ultrafast carrier dynamics of nanomaterials.

5.
Arch Microbiol ; 206(5): 232, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658486

RESUMO

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.


Assuntos
Anti-Inflamatórios não Esteroides , Biotransformação , Ibuprofeno , Naproxeno , Ibuprofeno/metabolismo , Naproxeno/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Biodegradação Ambiental
6.
Angew Chem Int Ed Engl ; 63(23): e202403245, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38578838

RESUMO

The encapsulation of functional colloidal nanoparticles (100 nm) into single-crystalline ZSM-5 zeolites, aiming to create uniform core-shell structures, is a highly sought-after yet formidable objective due to significant lattice mismatch and distinct crystallization properties. In this study, we demonstrate the fabrication of a core-shell structured single-crystal zeolite encompassing an Fe3O4 colloidal core via a novel confinement stepwise crystallization methodology. By engineering a confined nanocavity, anchoring nucleation sites, and executing stepwise crystallization, we have successfully encapsulated colloidal nanoparticles (CN) within single-crystal zeolites. These grafted sites, alongside the controlled crystallization process, compel the zeolite seed to nucleate and expand along the Fe3O4 colloidal nanoparticle surface, within a meticulously defined volume (1.5×107≤V≤1.3×108 nm3). Our strategy exhibits versatility and adaptability to an array of zeolites, including but not restricted to ZSM-5, NaA, ZSM-11, and TS-1 with polycrystalline zeolite shell. We highlight the uniformly structured magnetic-nucleus single-crystalline zeolite, which displays pronounced superparamagnetism (14 emu/g) and robust acidity (~0.83 mmol/g). This innovative material has been effectively utilized in a magnetically stabilized bed (MSB) reactor for the dehydration of ethanol, delivering an exceptional conversion rate (98 %), supreme ethylene selectivity (98 %), and superior catalytic endurance (in excess of 100 hours).

7.
Environ Pollut ; 349: 123908, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38570157

RESUMO

Paddy Crusts (PC) play a pivotal role in the migration and transformation of heavy metals within paddy ecosystems, situated at the critical intersection of air, water, and soil. This study focused on PC samples from heavy metal-contaminated rice paddies in six southern Chinese provinces. It's the first time we've screened and quantified the impact of nutrition, physicochemical properties, and heavy metals on bacterial diversity in PC. Our results highlight the significant influence of zinc, total nitrogen, and soil manganese on bacterial diversity. Using structural equation models, we identified the pathways through which these three types of environmental factors shape bacterial diversity. Heavy metal indicators and physical and chemical indicators exerted a direct negative effect on bacterial diversity in PC, while nutritional indicators had a direct and significant positive effect on bacterial diversity. Variance partitioning analysis revealed heavy metals had the most significant impact, accounting for 7.77% of the total effect. Moreover, the influence of heavy metals on bacterial diversity increased as diversity decreased, ranging from 3.81% to 42.09%. To remediate specific heavy metal pollution, our proposed method involves cultivating indigenous bacteria by controlling these environmental factors, based on an analysis of the interplay among bacterial diversity, environmental variables, and heavy metal bioconcentration factors. These findings enhance our understanding of PC and provide insights into rice field heavy metal pollution mitigation.


Assuntos
Metais Pesados , Oryza , Microbiologia do Solo , Poluentes do Solo , Metais Pesados/análise , China , Poluentes do Solo/análise , Bactérias/efeitos dos fármacos , Monitoramento Ambiental/métodos , Ecossistema , Solo/química , Agricultura
8.
Artigo em Inglês | MEDLINE | ID: mdl-38568773

RESUMO

Alzheimer's Disease (AD) accounts for the majority of dementia, and Mild Cognitive Impairment (MCI) is the early stage of AD. Early and accurate diagnosis of dementia plays a vital role in more targeted treatments and effectively halting disease progression. However, the clinical diagnosis of dementia requires various examinations, which are expensive and require a high level of expertise from the doctor. In this paper, we proposed a classification method based on multi-modal data including Electroencephalogram (EEG), eye tracking and behavioral data for early diagnosis of AD and MCI. Paradigms with various task difficulties were used to identify different severity of dementia: eye movement task and resting-state EEG tasks were used to detect AD, while eye movement task and delayed match-to-sample task were used to detect MCI. Besides, the effects of different features were compared and suitable EEG channels were selected for the detection. Furthermore, we proposed a data augmentation method to enlarge the dataset, designed an extra ERPNet feature extract layer to extract multi-modal features and used domain-adversarial neural network to improve the performance of MCI diagnosis. We achieved an average accuracy of 88.81% for MCI diagnosis and 100% for AD diagnosis. The results of this paper suggest that our classification method can provide a feasible and affordable way to diagnose dementia.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Redes Neurais de Computação , Diagnóstico Precoce
9.
J Nanobiotechnology ; 22(1): 140, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556857

RESUMO

BACKGROUND: Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. RESULTS: In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal "International Journal of Nanomedicine" has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. "Traditional Chinese medicine," "drug delivery," and "green synthesis" are the main research focal points. Themes such as "green synthesis," "curcumin," "wound healing," "drug delivery," and "carbon dots" may represent emerging research areas. CONCLUSIONS: Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine.


Assuntos
Nanopartículas , Plantas Medicinais , Humanos , China , Bibliometria , Extratos Vegetais
10.
Environ Res ; 252(Pt 3): 119025, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38685292

RESUMO

The control of carbon emissions from agriculture is imperative in addressing the challenges posed by the greenhouse effect. China must develop a specific pathway for reducing its agricultural carbon emissions, accounting for its unique circumstances and considering the impacts of trade liberalization. (1) The study revealing that agricultural trade liberalization (ATL) has a marked effect on lowering China's agricultural carbon emission intensity (ACEI), with robustness and endogeneity tests supporting these findings. (2) In the pursuit of emissions reduction, the crucial role of technology spillovers (TS) and the optimization of industrial structure (OIS) are essential. (3) The reduction in ACEI is particularly notable in coastal regions, areas with low environmental regulations and during periods characterized by more stable agricultural tariffs. This study shows a synergistic association between ATL and ACEI, indicates the potential for a mutually beneficial situation with advantages in both economic and environmental aspects.

11.
Diabetes Obes Metab ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618970

RESUMO

AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.

12.
Sci Total Environ ; 927: 172251, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604355

RESUMO

Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.


Assuntos
Bacteroides , Microbioma Gastrointestinal , Genoma Bacteriano , Simbiose , Microbioma Gastrointestinal/genética , Bacteroides/genética , Bacteroides/fisiologia , Humanos , Evolução Molecular , Transferência Genética Horizontal
13.
Int J Oral Sci ; 16(1): 29, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622125

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Prognóstico , Biomarcadores , Neoplasias de Cabeça e Pescoço/terapia , Análise de Célula Única , Microambiente Tumoral
14.
Nat Commun ; 15(1): 2818, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561369

RESUMO

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.


Assuntos
Macrófagos Associados a Tumor , Neoplasias da Bexiga Urinária , Animais , Masculino , Camundongos , Eferocitose , Evasão da Resposta Imune , Macrófagos/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Neoplasias da Bexiga Urinária/metabolismo
15.
Front Public Health ; 12: 1358290, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525328

RESUMO

Purpose: The detrimental effects of environmental tobacco smoke (ETS) on women's reproductive health have been widely recognized. However, the detailed association between exposure to environmental tobacco smoke and the incidence of infertility remains under-explored. This investigation focuses on exploring this potential connection. Methods: For this analysis, we extracted data from the US National Health and Nutrition Examination Survey (NHANES) database, covering the years 2013 to 2018, focusing on individuals with recorded serum cotinine levels and infertility information. ETS exposure and fertility status were analyzed as independent and dependent variables, respectively. We applied weighted multivariate logistic regression method to evaluate the impact of ETS on infertility, including subgroup analyses for more detailed insights. Results: The study encompassed 3,343 participants. Logistic regression analysis revealed a notable positive correlation between ETS exposure and infertility, with an odds ratio (OR) of 1.64 (95% Confidence Interval [CI]: 1.14-2.36). We observed a non-linear relationship between ETS exposure and infertility risk. Notably, infertility risk increased by 64% in serum cotinine levels above 0.136 compared to that in serum cotinine levels below 0.011. Further, subgroup analysis and interaction tests showed consistent results across different segments, underscoring the robustness of the ETS-infertility link. Conclusion: Our findings suggest that environmental tobacco smoke exposure may be a contributing factor to infertility. These results reinforce the recommendation for women in their reproductive years to avoid ETS exposure, especially when planning for pregnancy.


Assuntos
Infertilidade , Poluição por Fumaça de Tabaco , Gravidez , Humanos , Feminino , Estados Unidos/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/análise , Inquéritos Nutricionais , Cotinina/análise
16.
Microbiol Spectr ; 12(4): e0391823, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38441474

RESUMO

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant Escherichia coli T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR). Azithromycin enzyme-linked immunosorbent assay (ELISA) test, ompC gene overexpression, and molecular docking were utilized to conduct the confirmatory research of the potential mechanisms. We found that colistin combined with azithromycin led to 48 differentially expressed genes, compared to azithromycin alone, such as downregulation of tolA, eptB, lpxP, and opgE and upregulation of ompC gene. Interestingly, the addition of colistin to azithromycin differentially downregulated the mph(A) gene mediating azithromycin resistance, facilitating the intracellular accumulation of azithromycin. Also, overexpression of the ompC elevated azithromycin susceptibility, and colistin contributed to further suppression of the Mph(A) activity in the presence of azithromycin. These findings suggested that colistin firstly enhanced the permeability of bacterial OM, causing intracellular drug accumulation, and then had a repressive effect on the Mph(A) activity along with azithromycin. Our study provides a novel perspective that the improvement of azithromycin susceptibility is related not only to the downregulation of the mph(A) gene and conformational remodeling of the Mph(A) protein but also the upregulation of the membrane porin gene ompC.IMPORTANCEUsually, active efflux via efflux pumps is an important mechanism of antimicrobial resistance, such as the AcrAB-TolC complex and MdtEF. Also, bacterial porins exhibited a substantial fraction of the total number of outer membrane proteins in Enterobacteriaceae, which are involved in mediating the development of the resistance. We found that the upregulation or overexpression of the ompC gene contributed to the enhancement of resistant bacteria to azithromycin susceptibility, probably due to the augment of drug uptakes caused and the opportunity of Mph(A) function suppressed by azithromycin with colistin. Under the combination of colistin and azithromycin treatment, OmpC exhibited an increased selectivity for cationic molecules and played a key role in the restoral of the antibiotic susceptibility. Investigations on the regulation of porin expression that mediated drug resistance would be important in clinical isolates treated with antibiotics.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Azitromicina/farmacologia , Colistina/farmacologia , Regulação para Cima , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Porinas/genética , Porinas/metabolismo , Testes de Sensibilidade Microbiana , Proteínas de Escherichia coli/metabolismo
17.
Eur Arch Otorhinolaryngol ; 281(6): 3157-3166, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503971

RESUMO

PURPOSE: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). METHODS: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). CONCLUSION: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.


Assuntos
Neoplasias Orofaríngeas , Programa de SEER , Humanos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Medição de Risco , Infecções por Papillomavirus/radioterapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Pontuação de Propensão , Estudos Retrospectivos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia
18.
Heliyon ; 10(6): e27622, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515733

RESUMO

Polygalae radix (PR) is a famous herbal medicine obtained by drying the root of Polygala tenuifolia Willd., one of the traditional Chinese medicines (TCM) that can be used for healthy food. There are three main processed methods of PR, including removing the xylem of roots (Polygalae Cortex, PC), frying PC with licorice (LP), and frying PC with honey (HP). While processing is believed to enhance efficacy and reduce toxicity, it is crucial to understand the differences in chemical composition and biological activities between crude and processed PR. This study used ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) combined with multivariate statistical analysis to analyze the chemical profiles and differences between the crude and processed products. Total polyphenol contents (TPC), total flavonoid contents (TFC), total saponin contents (TSC) and antioxidant activity of the processed and crude PR were also investigated. A total of 131 chemical compounds, including 42 saponins, 44 oligosaccharide esters, 25 xanthones, 2 organic acids, 3 Carbohydrates, and 15 components detected in auxiliary materials, were detected in all samples. Notably, PC exhibited significant changes among the three processed products, with the content of 62 compounds being higher. Processing of licorice (LP) and honey (HP) decreased the content of several compounds due to temperature and moisture influences. Comprehensive comparison of the antioxidant capacity of crude and processed PR showed that the antioxidant capacity of PC was higher than that of PR, HP, and LP. Our results can provide a scientific basis for further developing and applying P. tenuifolia resources.

19.
Clin Cosmet Investig Dermatol ; 17: 637-647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505806

RESUMO

Aim: Mycobacterium abscessus is ubiquitous in the environment and seldom causes infections in immunocompetent individuals. However, skin and soft tissue infections caused by M. abscessus have been reported in recent years. Additionally, the cutaneous infections or outbreaks post cosmetic surgery caused by M. abscessus have been increasing due to the popularity of plastic surgery. The main modes of transmission are through contaminated saline, disinfectants, or surgery equipment, as well as close contact between patients. This article describes three patients who were admitted to our hospital between November 2019 and October 2020. They presented with long-term non-healing wounds caused by M. abscessus infection after undergoing plastic surgery. Symptoms presented by the three patients included swelling, ulceration, secretion, and pain. After identification of M. abscessus with Ziehl-Neelsen staining and MALDI-TOF MS system, the patients were treated with surgical debridement and clarithromycin. Conclusion: It is important to note that a long-term wound that does not heal, especially after plastic surgery, should raise suspicion for M. abscessus infection. The infection mechanism in these three patients may have been due to exposure to surgical equipment that was not properly sterilized or due to poor sterile technique by the plastic surgeon. To prevent such infections, it is important to ensure proper sterilization of surgical equipment and saline.

20.
Environ Pollut ; 348: 123858, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554834

RESUMO

During the rice growth cycle, the average available cadmium concentration (CA-Cd) in the soil determines the Cd content in rice plant. Given defined soil properties and rice varieties, the meteorological factors play a crucial role in soil's available cadmium concentration (CCd) during the rice growth cycle. Thus, it is significant to investigate the influence of meteorological factors in CCd during the rice growth cycle and develop a predictive model for CA-Cd. The rice was cultivated under seven different sowing dates in Cd and As-contaminated soil in Hunan Province. Studied the impact of meteorological factors on paddy soil. The results showed that accumulated temperature (AT) and total precipitation (TP) were key factors affecting the soil CCd. The correlation coefficients between AT and TP with soil CA-Cd were 0.98 and -0.94 (p < 0.01), respectively. However, there was no significant correlation with CAs. AT mainly influenced the CCd during the grouting and maturity stages. A straightforward empirical prediction model was developed, capable of accurately forecasting CA-Cd during the rice growth cycle by considering meteorological factors and the initial soil CCd. This study supported a novel foundation for the precise prediction of Cd content in rice.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Poluentes do Solo/análise , Solo , Poluição Ambiental
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